Cannabinoid Modulation of Monoamine Levels in Mouse Brain:Unveiling Neurochemical Dynamics through an Innovative High-performance Liquid Chromatography-Fluorescence Detection Bioanalysis
摘要 Homeostasis of monoaminergic pathways is compromised in aging and neurodegenerative/neurological diseases such as Alzheimer's disease and depression.On the other hand,their modulation has also been linked to the mechanism of action of several drugs.Therefore,monitoring the levels of noradrenaline(NA),adrenaline(AD),dopamine(DA),and serotonin(5-HT),as well as those of tryptophan(TRYP),the precursor of 5-HT,and DA metabolites,namely 3,4-dihydroxypheny-lacetic acid(DOPAC)and homovanillic acid(HVA),is fundamental for assessing disease severity and progression.This work aimed to develop and validate the first High-Performance Liquid Chromatography(HPLC)coupled with fluorescence detector(FLD)method that simultaneously and accurately quantifies NA,AD,DA,DOPAC,HVA,5-HT and TRYP in mouse brain and prefrontal cortex(PFC)matrices.Previous sample preparation by protein precipitation was required to extract the compounds.Calibration curves were plotted using the background subtraction approach to reduce the interfer-ence of the endogenous analytes.Intra and inter-day accuracy and precision were within the ranges defined by ICH(The International Council for Harmonisation)guideline for bioanalytical method validation.Following validation,the impact of cannabidiol(CBD),cannabigerol(CBG),and cannabidivarin(CBDV)was explored in mice brains post-administration,revealing significant alterations in specific neurotransmitter levels upon cannabinoid exposure and shedding light on the complex modulation of neurochemical dynamics by cannabinoids.This research highlights the fit-for-purpose of the HPLC-FLD method and provides insights into potential mechanisms underlying phytocannabinoid actions in the central nervous system(CNS).
Author: Fonseca Carla Cunha Susana Ferreira Ricardo Lapo Pais Mariana Gonçalves Joana Camins Antoni Ettcheto Miren Barbosa Rui Fortuna Ana
作者单位: Laboratory of Pharmacology,Faculty of Pharmacy,University of Coimbra,Pólo das Ciências da Saúde,Azinhaga de Santa Comba,Coimbra 3000-548,Portugal CIBIT/ICNAS-Coimbra Institute for Biomedical Imaging and Translational Research,University of Coimbra,Coimbra 3000-548,Portugal Department of Pharmacology,Toxicology and Therapeutic Chemistry,Faculty of Pharmacy and Food Science,Universitat de Barcelona,Barcelona 08028,Spain Institute of Neurosciences,Universitat de Barcelona,Barcelona 08035,Spain Faculty of Sciences and Technology,Doctoral Program in Biomedical Engineering,University of Coimbra,Coimbra 3004-516,Portugal Biomedical Research Networking Centre in Neurodegenerative Diseases(CIBERNED),Carlos III Health Institute,Madrid 28031,Spain Institut d'Investigació Sanitària Pere Virgili(IISPV),Reus 43204,Spain CNC-Center for Neuroscience and Cell Biology,University of Coimbra,Coimbra 3004-504,Portugal
年,卷(期): 2024, 8(3)
机标分类号: S TP311 H3.1
在线出版日期: 2024年11月27日